Sangeeta Dhawan, Ph.D.

626-256-4673
Sangeeta Dhawan
Associate Professor, Department Of Translational Research & Cellular Therapeutics
Research Area
Epigenetics
Islet Development, Function, And Survival
Diabetes Pathogenesis
Beta-cell Regeneration
Research Teams
Translational Research & Cellular Therapeutics
Sangeeta Dhawan received her Ph.D. in molecular and developmental biology from Indian Institute of Science, Bangalore, India, where she studied the developmental regulation of silk gland formation in the silkworm Bombyx mori. She did her postdoctoral training at Harvard Medical School and UCLA.
 
Her training at UCLA focused on understanding the mechanisms of beta cell mass regulation. This work was supported by an advanced postdoctoral fellowship from JDRF. She is also a recipient of the Start-up Award and the Smookler Award for Diabetes Research from the Larry L. Hillblom Foundation, as well as a Transition Award from JDRF. She has served as a reviewer for journals such as Diabetes, and Regulatory Peptides.
Location
Education & Experience
Degrees

  • 1995 -1997, B.Sc., Biochemistry, Sri Venkateswara College, Delhi University, New Delhi, India

  • 1995 - 1997, M.Sc., Biochemistry, South Campus, Delhi University, New Delhi, India

  • 2003, Ph.D., Developmental biology of the silkgland in the silkworm Bombyx Mori, Indian Institute of Science, Bangalore, India

Fellowship

  • 2005 - 2008, Postdoctoral Fellow, Larry L. Hillblom Islet Research Center, Department of Medicine/Endocrinology University of California Los Angeles

  • 2004-2005, Post-doctoral Fellow, Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine

  • 2003-2004, Postdoctoral Fellow, Beth Israel Deaconess Medical, Center Harvard Medical School

Professional Experience

  • 2023-present, Associate Professor, Department of Translational Research and Cellular Therapeutics, Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA

  • 2017-2023, Assistant Professor, Department of Translational Research and Cellular Therapeutics, Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA

  • 2015-2017 Adjunct Associate Professor, Larry L. Hillblom Islet Research Center, Department of Medicine/Endocrinology University of California Los Angeles, Los Angeles, CA

  • 2008-2014 Assistant Researcher, Larry L. Hillblom Islet Research Center, Department of Medicine/Endocrinology University of California Los Angeles, Los Angeles, CA

Research

Research Area 

Epigenetic regulation of functional beta cell mass in health and disease

Overview

The Dhawan lab focuses on understanding the biology of insulin producing beta-cells. Both Type 1 and Type 2 diabetes are associated with the loss of pancreatic beta-cells, making the replacement of beta-cells an important therapeutic goal. Approaches to this end include generating beta-cells from stem cells, and protecting and reviving existing beta-cells. In pursuit of this, we study the epigenetic mechanisms that regulate the formation, function, regeneration and survival of beta-cells in homeostasis, and their failure in diabetes.  

PI Biography

Sangeeta Dhawan received her Ph.D. in molecular and developmental biology from Indian Institute of Science, Bangalore, India, where she studied the developmental regulation of silk gland formation in the silkworm Bombyx mori. She did her postdoctoral training at Harvard Medical School and UCLA. Her training at UCLA focused on understanding the mechanisms of beta cell mass regulation. This work was supported by an advanced postdoctoral fellowship from JDRF. She has been a recipient of the Start-up Award and the Smookler Award for Diabetes Research from the Larry L. Hillblom Foundation, a Transition Award from JDRF, and the Human Islet Research Network (HIRN) New Investigator Award. Dr. Dhawan is currently a standing member of the American Diabetes Association (ADA)’s Research Grant Review Committee, and has also served on NIH study section  Dr. Dhawan also serves as a reviewer for many high-impact journals such as Nature, Nature Communications, Science, Science Advances, Science Translation Medicine, Journal of Clinical Medicine, and Diabetes, and is currently an Associate Editor with Frontiers in Endocrinology. Research in Dhawan Lab is sponsored by the National Institutes of Health.
 

Dr. Dhawan's group is interested in understanding the biology of the insulin producing beta cells. Both type 1 and type 2 diabetes result from the loss of beta cells, making beta cell replenishment a very important therapeutic goal. Approaches to this end include generating beta cells from stem/iPS cells, as well as protecting and regenerating the endogenous beta cells. The successful outcome of each of these approaches demands the generation of abundant numbers of functional beta cells that are survival competent in the diabetic milieu. With this in mind, the research in Dhawan laboratory focuses on understanding the epigenetic and cellular signaling pathways that regulate the formation, function, regeneration and survival of pancreatic beta cells during development, and under circumstances that warrant the repair/regeneration of beta cells In addition, these studies aim to identify and characterize beta cell subpopulations and their role in glucose homeostasis. The Dhawan’s lab is also interested in the dyregulation of epigenetic processes in beta cells during diabetes pathogenesis. The Dhawan lab used mouse genetics, lineage tracing, islet culture and high throughput sequencing techniques to address these questions.
Lab Members
Nazia Parveen
Dr. Nazia Parveen
Postdoctoral Fellow
Postdoctoral Fellow: Dr. Parveen earned her PhD in Molecular Immunology from the Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India where she worked on investigating the role of bacterial proteins in regulating macrophage innate immune responses and antigen presentation. Her current work focuses on investigating the role of DNA methylation patterns in regulating beta cell identity and heterogeneity in health and diabetes.
Sneha Varghese
Dr. Sneha Varghese
Postdoctoral Fellow
Dr. Varghese did her Ph.D at the Department of Biotechnology at Indian Institute of Technology Kharagpur, in Molecular biology and Parasitology. Her Ph.D. studies focused on the role of the DNA-binding protein Topoisomerase-I in the human parasite Entamoeba histolytica stress-response during and investigating its potential as an anti-amebic therapeutic target. Her present work is aimed at understanding the epigenetic control of beta cell survival and stress response.
AHernandez
Giovanni Hernandez De La-Peña
Research Associate
Giovanni Hernandez De La-Peña- Research Associate: Giovanni is a recent graduate from the University of Arizona with a BS in Pharmaceutical Sciences. During his undergraduate career, he researched the effects of developmental nicotine exposure on neural respiratory signaling in the brainstem spinal cord. His current studies address the regulation of the mature islet phenotype in early neonatal life.
Key Research Projects

• Epigenetic control of endocrine cell fate specification and maintenance: We aim to understand the epigenetic regulation of beta cell identity, heterogeneity, and maturity in health and diabetes. A special point of interest for us is the regulation of islet intrinsic neuronal-like features.

• Developmental epigenetic patterns underlying beta cell fitness and implication for diabetes risk: We are very interesting in the developmental origins of diabetes and the underlying molecular mechanisms, key among them being the DNA methylation and hydroxy-methylation blueprints of beta cell phenotype.

• Epigenetic control of beta cell function, survival, and  senescence: We are focusing on how 3D chromatin architecture defines the transcriptional programs that co-direct beta cell function and health, and their relevance to beta cell adaptation to stress. 
 

Dhawan research
Lab Publication Highlights
  • Spaeth JM, Dhawan S. The Yin and Yang of Modulating β-Cell DNA Damage Response and Functional Mass. Diabetes. 2022 Aug 1;71(8):1614-1616. doi: 10.2337/dbi22-0010.
  • Filipowska J, Kondegowda NG, Leon-Rivera N, Dhawan S, Vasavada RC. LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation. Front. Endocrinol (Lausanne). 2022;13:867001. doi: 10.3389/fendo.2022.867001
  • Varghese SS, Dhawan S. Polycomb Repressive Complexes: Shaping Pancreatic Beta-Cell Destiny in Development and Metabolic Disease. Front Cell Dev Biol. 2022;10:868592. doi: 10.3389/fcell.2022.868592.
  • Georgia S, Arda HE, Martinez-Sanchez A, Dhawan S. Editorial: Epigenetics of Glucose Homeostasis. Front Endocrinol (Lausanne). 2022;13:889189. doi: 10.3389/fendo.2022.889189. eCollection 2022.
  • Parveen N, Dhawan S. DNA Methylation Patterning and the Regulation of Beta Cell Homeostasis. Front Endocrinol (Lausanne). 2021;12:651258. doi: 10.3389/fendo.2021.651258. eCollection 2021.
  • Rakshit K, Qian J, Gaonkar KS, Dhawan S, Colwell CS, Matveyenko AV. Postnatal Ontogenesis of the Islet Circadian Clock Plays a Contributory Role in β-Cell Maturation Process. Diabetes. 2018;67(5):911-922.
  • Rodnoi P., Rajkumar M., Md Moin A.S., Georgia S.K., Butler A.E., Dhawan S. Neuropeptide Y expression marks partially differentiated beta-cells in mice and humans. JCI Insight. 2017; 2(12). doi: 10.1172/jci.insight.94005
  • Dhawan S., Dirice E., Kulkarni R.N., Bhushan A. Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication. Diabetes. 2016; 65(5):1208-18.
  • Dhawan, S., Tschen, S.I., Zeng, C., Guo, T., Hebrok, M., Matveyenko, A., Bhushan, A. DNA methylation directs functional maturation. Of pancreatic beta cells. Journal of Clinical Investigation. 2015; 125(7): 2851-2860.
  • Zhou, X., Dhawan, S., Fu H., Kundu, S., Kim, S.K., Bhushan, A. Polycomb and trithorax regulation of Ink4a to regenerate beta cells. Journal of Clinical Investigation. 2013;  123 (11): 4849-4858.
  • Papizan, J.B., Singer, R.A*., Tschen, S.I.*. Dhawan, S*., Friel, J.M., Hipkins, S.B., Magnuson, M.A., Bhushan, A., Sussel., L. Nkx2.2 repressor complex regulates islet beta cell specification and prevents beta to alpha cell reprogramming. Genes and Development. 2011; 25(21): 2291-2305.
  • Dhawan, S., Georgia, S., Tschen, S.I., Bhushan A. Pancreatic beta cell identity is maintained by DNA methylation-mediated repression of Arx. 2011; Developmental Cell. 20 (4): 419-429.
  • Dhawan, S., Tschen, S.I., Bhushan A. Bmi-1 regulates Ink4a/Arf locus to control pancreatic beta cell proliferation. Genes and Development. 2009; 23(8):906-11.
  • Tschen, S. I., Dhawan, S., Gurlo T., Bhushan A. (2009) Age-dependent decline in beta cell proliferation restricts the capacity of beta cell regeneration in mice. Diabetes. 2009; 58(6):1312-20.
     
Publications
  • Rodnoi P., Rajkumar M., Md Moin A.S., Georgia S.K., Butler A.E., Dhawan S. Neuropeptide Y expression marks partially differentiated beta-cells in mice and humans. JCI Insight. 2017; 2(12).
  • Dhawan S., Dirice E., Kulkarni R.N., Bhushan A. Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication. Diabetes. 2016; 65(5):1208-18.
  • Dhawan, S., Tschen, S.I., Zeng, C., Guo, T., Hebrok, M., Matveyenko, A., Bhushan, A. (2015)  DNA methylation directs functional maturation. Of pancreatic beta cells. Journal of Clinical Investigation. 125(7): 2851-2860.
  • Zhou, X., Dhawan, S., Fu H., Kundu, S., Kim, S.K., Bhushan, A. (2013) Polycomb and trithorax regulation of Ink4a to regenerate beta cells. Journal of Clinical Investigation. 123 (11): 4849-4858.
  • Papizan, J.B., Singer, R.A*., Tschen, S.I.*. Dhawan, S*. , Friel, J.M., Hipkins, S.B., Magnuson,  M.A., Bhushan, A., Sussel., L. (2011) Nkx2.2 repressor complex regulates islet  beta cell  specification and prevents beta to alpha cell reprogramming. Genes and Development . 25(21): 2291-2305.
  • Dhawan, S., Georgia, S., Tschen, S.I., Bhushan A. (2011) Pancreatic beta cell identity is  maintained by DNA methylation-mediated repression of Arx . Developmental Cell. 20  (4): 419-429.
  • Dhawan, S., Tschen, S.I., Bhushan A. (2009) Bmi-1 regulates Ink4a/Arf locus to  control pancreatic beta cell proliferation. Genes and Development. 23(8):906-11.
  • Tschen, S. I., Dhawan, S., Gurlo T., Bhushan A. (2009) Age-dependent decline in beta cell proliferation restricts the capacity of beta cell regeneration in mice. Diabetes 58(6):1312-20.